PT-141 — Canada Research Brief

Origin and development

PT-141 emerged from Palatin Technologies' melanocortin programme in the early 2000s as a deliberate spin-out of the melanotan-2 research line. The observation that drove the programme was simple: MT-II's sexual-function effects were mediated by central MC4R activation, not by the pigmentation-focused MC1R activity that had motivated the original University of Arizona work. Palatin synthesised the free-acid analogue — structurally identical to MT-II except that the C-terminal amide is replaced by a carboxylate — and found it retained MC4R activity with a cleaner receptor profile.

The compound was first developed as an intranasal spray, but that formulation was discontinued after blood-pressure signals in trials. Palatin pivoted to a subcutaneous auto-injector, which ultimately received FDA approval in June 2019 as Vyleesi for hypoactive sexual desire disorder in premenopausal women.

Clinical evidence

The pivotal evidence is the RECONNECT programme — two identical Phase 3 trials reported by Kingsberg and colleagues in Obstetrics and Gynecology (2019). Premenopausal women with acquired, generalised HSDD self-administered 1.75 mg subcutaneous bremelanotide approximately 45 minutes before anticipated sexual activity. Both trials showed statistically significant improvements on the Female Sexual Function Index desire domain and on distress scores versus placebo, with nausea and injection-site reactions as the dominant adverse events. Approval is US-only; Health Canada has not authorised bremelanotide for any indication.

Mechanism note

Unlike PDE5 inhibitors — which act peripherally on vascular smooth muscle — bremelanotide acts centrally. MC4R is expressed in hypothalamic nuclei implicated in sexual motivation, and the hypothesised mechanism is activation of those central circuits rather than any direct vasodilatory effect. The pharmacology is continuous with MT-II's but with a narrower receptor profile.

Storage

Store lyophilised PT-141 at −20°C protected from light. Reconstituted peptide is stable refrigerated at 2–8°C for 2–4 weeks.